The dynamic shape undulations of a moving cell’s leading edge, increasing in time from blue to red. Image credit: Rikki Garner and Julie Theriot (CC BY 4.0)
In every human cell, there are tens of millions of proteins which work together to control everything from the cell’s shape to its behavior. One of the most abundant proteins is actin, which organizes itself into filaments that mechanically support the cell and help it to move.
These filaments are very dynamic, with individual actin molecules constantly being added or removed. This allows the cell to build large structures with distinct shapes and properties. Many motile cells, for example, have a structure called a lamellipodium which protrudes at their ‘leading edge’ and pushes them forward. The lamellipodium has a very robust shape that does not vary much between different cell types, or change significantly as cells migrate. But how the tens of thousands of actin molecules inside the lamellipodium organize themselves into this large, stable structure is not fully understood.
To investigate, Garner and Theriot used high-speed video microscopy to track the shape of human cells cultured in the laboratory. As the cells crawled along a glass surface, their leading edge undulated like strings being plucked on a guitar. A computer simulation showed that these ripples can be caused by filaments randomly adding and removing actin molecules.
While these random movements could destabilize the structure of the leading edge, the simulation suggests that another aspect of actin filament growth smooths out any fluctuations in the lamellipodium’s shape. Actin networks in the lamellipodium have a branched configuration, with new strands emerging off each other at an angle like branches in a tree. Garner and Theriot found that the specific angle in which new filaments are added smooths out the lamellipodium’s shape, which may explain why this geometry has persisted throughout evolution.
These findings suggest that the way in which actin filaments join together helps to maintain the shape of large cellular structures. In the future, scientists could use this design principle to build molecular machines that can self-organize into microstructures. These engineered constructs could be used to modulate the activity of living cells that have been damaged by disease.
